Biology of insulin‐like growth factors in development

Abstract

Insulin-like growth factors (IGFs) provide essential signals for the control of embryonic and postnatal development in vertebrate species. In mammals, IGFs act through and are regulated by a system of receptors, binding proteins, and related proteases. In each of the many tissues dependent on this family of growth factors, this system generates a complex interaction specific to the tissue concerned. Studies carried out over the last decade, mostly with transgenic and gene knockout mouse models, have demonstrated considerable variety in the cell type-specific and developmental stage-specific functions of IGF signals. Brain, muscle, bone, cartilage, pancreas, ovary, skin, and fat tissue have been identified as major in vivo targets for IGFs. Concentrating on several of these organ systems, we review here phenotypic analyses of mice with genetically modified IGF systems. Much progress has also been made in understanding the specific intracellular signaling cascades initiated by the binding of circulating IGFs to their cognate receptor. We also summarize the most relevant aspects of this research. Considerable efforts are currently focused on deciphering the functional specificities of intracellular pathways, particularly the molecular mechanisms by which cells distinguish growth-stimulating insulin-like signals from metabolic insulin signals. Finally, there is a growing body of evidence implicating IGF signaling in lifespan control, and it has recently been shown that this function has been conserved throughout evolution. Very rapid progress in this domain seems to indicate that longevity may be subject to IGF-dependent neuroendocrine regulation and that certain periods of the life cycle may be particularly important in the determination of individual lifespan.

Treating Human Meniscal Fibrochondrocytes with hIGF-1 Gene by Liposome

“…Several studies confirm human insulin-like growth factor-1 (hIGF-1) plays a key role in the regulation of chondrocyte proteoglycan metabolism and stimulates cell proliferation [5,12,16,17]. Theoretically, then, human meniscal fibrochondrocytes cultured in vitro may present a positive response to liposome-mediated hIGF-1 gene transfection.…”

“…It also plays an important role in stimulating collagen and proteoglycan synthesis in cartilage through an autocrine feedback mechanism [25]. Since hIGF-1 is a major chondro-enhancing agent, notwithstanding its attenuated effect on aged cartilage, it would appear a logical choice for gene therapy approaches [4,5,7,12,16]. It is a relatively small gene of approximately 45 kb pairs with the transcribed region spanning less than 1 kb, and the DNA sequence is known in most species.…”

“…Human insulin-like growth factor-1 (hIGF-1) stimulates the synthesis and deposition of extracellular matrix components by chondrocytes as well as cell proliferation [5,12,16]. In cell culture, it suppresses chondrocyte dedifferentiation and stabilizes the chondrocyte phenotype [17].…”

Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto–Kakizaki rat model of type 2 diabetes

“…Indeed, the importance of the IGF system for beta cell development in vivo has been well demonstrated in physiological studies of genetically modified animals (reviewed in [8,9]). Igf2 overexpression in transgenic mice has a profound effect on pancreas morphology and causes islets hyperplasia [11].…”

“…Evidence for the involvement of the IGF family in beta cell development is abundant and based on physiological studies [7] and genetic mouse models [7][8][9] as follows: (1) IGFs are mitogenic for beta cells [7]; (2) IGFs and their binding proteins are produced in fetal and adult pancreata [10]; (3) IGFs act as cell survival factors by inhibiting beta cell apoptosis [7]; (4) IGF2 overexpression in transgenic mice causes islet hyperplasia [11]; and (5) undernourished fetuses with an increased beta cell mass have locally increased pancreatic Igf1 expression [12].…”